CROI 2025 Abstract eBook

Abstract eBook

Oral Abstracts

201

Tecovirimat Is Safe but Not Efficacious in People With Clade II Mpox Timothy Wilkin 1 , William A. Fischer II 2 , Lu Zheng 3 , Caitlyn McCarthy 3 , Pooja Saha 3 , Arzhang Javan 4 , Alexander L. Greninger 5 , Kristina Brooks 6 , Rachel A. Bender Ignacio 5 , Annie F. Luetkemeyer 7 , Joseph J. Eron 2 , Rajesh T. Gandhi 8 , Sharon Nachman 9 , Judith Currier 10 , Jason Zucker 11 , for the ACTG A5418 Study Team 1 University of California San Diego, La Jolla, CA, USA, 2 University of North Carolina at Chapel Hill, Chapel Hill, NC, USA, 3 Harvard TH Chan School of Public Health, Boston, MA, USA, 4 National Institutes of Health, Bethesda, MD, USA, 5 University of Washington, Seattle, WA, USA, 6 University of Colorado Anschutz Medical Campus, Aurora, CO, USA, 7 University of California San Francisco, San Francisco, CA, USA, 8 Harvard Medical School, Boston, MA, USA, 9 Stony Brook University, Stony Brook, NY, USA, 10 University of California Los Angeles, Los Angeles, CA, USA, 11 Columbia University Irving Medical Center, New York, NY, USA Background: Mpox has caused two international public health emergencies; no therapies have established efficacy. ACTG A5418/STOMP is a phase 3 randomized placebo-controlled double-blind trial evaluating the efficacy of tecovirimat, an antiviral with animal data supporting its use for orthopox infections. Methods: Participants ≥18 years with symptomatic laboratory-confirmed or presumptive mpox <14 days were randomized 2:1 to oral tecovirimat 600mg twice daily or placebo for 14 days. Participants with or at risk for severe disease, pregnant women and children were enrolled in an open-label arm. The primary outcome was time to clinical resolution (all skin lesions scabbed, desquamated, or healed, and visible mucosal lesions healed) by Day 29. The secondary outcome included mean pain score reduction over 5 days, and longitudinal mpox DNA changes from a representative skin lesion for those enrolled in person. In November 2024, the Data and Safety Monitoring Board recommended stopping randomization based on a futility analysis. Results: Of 412 eligible participants randomized to tecovirimat (275) or placebo (137) at 50 sites in 7 countries, 24% were enrolled remotely, 98% were male, 97% were cisgender, and median age was 34 years; 53% white, 11% black, 45% Hispanic; 33% living with HIV; 22% had received ≥1 dose of mpox vaccine. At entry median symptom duration was 8 days (IQR 5,10), median lesion number was 9 (IQR 4, 19; max 242), 33% had severe pain (7-10 on 11-point scale); 68 (17%) did not have mpox diagnosed and were excluded. By Day 29, the estimated cumulative incidence of clinical resolution was 83% and 84%, respectively (instantaneous risk ratio 0.98, nominal 98.1% CI: 0.74-1.31; p=0.89) ( Figure ). Receipt of open-label tecovirimat due to disease progression or persistent severe pain was the same (7% in each arm). Adverse events were similar (11% vs. 9%). Among those with severe pain at baseline (a pre-specified analysis), mean [sd] pain score reduction was similar for tecovirimat (3.2 [2.1]) and placebo (3.1 [2.0]). More participants in tecovirimat arm had undetectable mpox DNA at Day 8 (48%) compared to placebo (33%) but no meaningful difference at Day 15 (83% and 78% respectively). Conclusions: Tecovirimat did not reduce clinical resolution of mpox lesions or improve pain control among adults with clade II mpox. These results do not support the continued use of tecovirimat monotherapy for mpox.

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Randomized Trial of Long-Acting Cabotegravir and Rilpivirine in Africa (CARES): Week 96 Results Cissy Kityo 1 , Ivan K. Mambule 1 , Simiso M. Sokhela 2 , Reena Shah 3 , Joseph Musaazi 4 , Caroline Otike 1 , Henry Mugerwa 1 , Fiona Cresswell 5 , Charity Wambui 6 , Ibrahim Yawe 7 , Josphat Kosgei 8 , Logashvari N. Naidoo 9 , Veerle Van Eygen 10 , Fafa A. Boateng 11 , Nicholas Paton 5 , for the CARES Trial Team 1 Joint Clinical Research Centre, Kampala, Uganda, 2 Ezintsha, Johannesburg, South Africa, 3 Aga Khan University Hospital, Nairobi, Kenya, 4 Infectious Diseases Institute, Kampala, Uganda, 5 London School of Hygiene & Tropical Medicine, London, UK, 6 Moi University, Eldoret, Kenya, 7 Joint Clinical Research Centre, Fort Portal, Uganda, 8 Walter Reed Project–Kericho, Kericho, Kenya, 9 South African Medical Research Council, Cape Town, South Africa, 10 Johnson & Johnson, Beerse, Belgium, 11 Johnson & Johnson Middle East, Accra, Ghana Background: Evidence is required to support use of long-acting injectable therapy (LA) in Africa, where demographic factors, viral subtypes, prior treatment, archived drug resistance, and approaches to treatment delivery and monitoring differ from resource-rich settings. We previously reported non inferior efficacy of LA versus oral antiretroviral therapy (ART) at 48 weeks, but longer-term data are needed to assess durability in program settings. Methods: This randomized, multicentre, open-label trial evaluated efficacy, safety, and tolerability of switching from oral ART to LA. Adults with HIV-1, stable on first-line oral ART (TDF +3TC/FTC+EFV/NVP/DTG) with screening VL <50 copies/ml were enrolled at 8 African sites. Main exclusion criteria were past virologic failure, current pregnancy and HBV co-infection. Participants were randomized (1:1) to continue oral ART (OT group) or switch to cabotegravir (CAB)+rilpivirine (RPV) intramuscular injections every 8 weeks (LA group). VL was monitored every 24 weeks. Main outcome is % participants with VL <50 copies/ml at week 96 (FDA snapshot; non-inferiority margin 10%). Confirmed virologic failure (CVF, secondary outcome) was defined as 2 consecutive VL ≥200 copies/ml. Subtype and resistance mutations were determined at baseline in all (archived DNA, retrospective), and at CVF (real-time, RNA). Results: 512 participants were enrolled (median age 42y; 58% female; 92% on DTG-based ART; 74% with prior NNRTI exposure; 8% baseline archived RPV resistance mutations [in sequences without APOBEC mutations]; 57% viral subtype A1; 21% baseline BMI ≥30kg/m 2 ). Seven withdrew (3 LA, 4 OT group) and two died (1LA, 1OT) by week 96. At 96 weeks, 247/255 (96.9%) in LA and 250/257 (97.3%) in OT group had VL<50 copies/mL (difference -0.4%; 95%CI -3.1 to 2.0%); demonstrating non-inferiority (Table). Four participants (1.6%) in LA group and none in OT group had CVF by week 96; 3 resuppressed on TDF/3TC/ DTG. Adverse events of grade ≥3 severity occurred in 41 (16%) in LA and 22 (9%) in OT group; only one treatment-related adverse event in the LA group led to treatment discontinuation (injection-site abscess). Conclusions: At 96 weeks, CAB and RPV LA showed high efficacy, non-inferior to oral ART when used in the public health approach with sparse VL monitoring and without real-time baseline resistance testing. CVF and acquired resistance was uncommon. LA was effective with an acceptable safety profile and may be considered for use in treatment programs in sub-Saharan Africa.

Oral Abstracts

57

CROI 2025